The goal of this renewal proposal is to continue developing Monte Carlo software tools for intensity modulated radiation therapy (IMRT) and other advanced external beam treatment techniques for 3-dimensional conformal radiation therapy (3DCRT). Although IMRT has received general acceptance and has been routinely used in some cancer clinics there are potential stumbling blocks in the clinical implementation and widespread use of IMRT and other advance treatment techniques for 3DCRT. We hypothesize that the use of a set of advanced Monte Carlo tools in IMRT plan verification and beam delivery will provide significant improvement in the quality assurance (QA) of routine IMRT treatments, which will lead to the safe, reliable and efficient application of these new techniques. The specific aims of this proposal are: (1) Develop practical source modeling and beam commissioning tools for Monte Carlo dose calculation. We will show that measurement-based source models can be used to produce reliable dose distributions for both phantom and patient dosimetry verification as those produced by Monte Carlo simulated phase space data. We will develop generic source models for the IMRT beams from commonly used clinical accelerators. We will develop practical software tools for Monte Carlo beam commission using these source models based on a standard set of measured beam data. (2) Develop Monte Carlo-based MU/plan verification tools for IMRT QA. We will develop practical Monte Carlo dose calculation tools for IMRT monitor unit (MU) and treatment plan verification. The tools will be reliable, efficient and easy to implement for routine clinical QA applications. We will develop software interfaces to integrate the plan verification tool into the IMRT treatment planning and beam delivery environment. The MU calculation tool will be developed as an independent dosimetry check for individual patient treatment QA. (3) Apply Monte Carlo simulations for retrospective/prospective studies. We will investigate the impact of improved dosimetry accuracy on the outcome of clinical trials. We will compare dose distributions calculated by our Monte Carlo dose verification tools and existing treatment planning systems for retrospective and prospective studies. Effects produced by dose calculation uncertainty, organ motion and patient setup on IMRT treatment will be measured using dose volume histogram (DVH), isodose distributions and other physical dose parameters, as well as biological parameters including tumor control probability (TCP) and normal tissue complication probability (NTCP). The results will be used as reference materials in retrospective studies as well as ongoing clinical trials.